Tulobuterol functions to selectively stimulate .beta..sub.2 -receptors of the sympathetic nerves to show a bronchodilatory action. This drug is widely used in the treatment of chronic bronchitis, bronchial asthma, and the like in order to relieve dyspnea of the patients suffering from air way stricture.
Generally employed methods for administering tulobuterol to the living body include oral administration in the form of tablets, dry syrup, etc. However, the oral administration has problems, for example, that administration to infants and the like is difficult, the blood level of the drug increases rapidly to produce severe side effects, and the efficacy duration is short. To overcome these problems, an adhesive preparation of tulobuterol is proposed as described in JP-A-4-99720 (the term "JP-A" as used herein means an "unexamined published Japanese patent application"). Adhesive preparations have an advantage that since the drug is percutaneously administered, administration to infants and like is easy and the drug is rapidly absorbed through the skin. Such preparations are also advantageous in that efficacy duration can be attained and side effects can be diminished.
In an adhesive preparation containing tulobuterol, the tulobuterol contained in the plaster layer, which comes into contact with a skin surface, is present in a crystalline state or dissolved state depending on the saturation solubility thereof in the plaster layer. When this adhesive preparation is applied to a skin surface, the tulobuterol in a dissolved state (hereinafter also referred to as "dissolved tulobuterol") speedily migrates to the skin and is absorbed as long as the dissolved tulobuterol is not trapped, e.g., by the pressure-sensitive adhesive contained in the plaster layer as a result of ionic bonding with functional groups of the adhesive, although the tulobuterol in a crystalline state (hereinafter also referred to as "crystalline tulobuterol") does not participate in percutaneous absorption. Hence, the higher the content of dissolved tulobuterol in the plaster layer, the larger the amount of percutaneously absorbed tulobuterol and the longer the efficacy duration. Consequently, investigations are usually directed to developments of adhesive preparations containing dissolved tulobuterol.
In other words, the above means that the pharmacologically-active-duration time for tulobuterol is limited by the saturation solubility of tulobuterol in the pressure-sensitive adhesive. Therefore, use of a pressure-sensitive adhesive in which tulobuterol has a low solubility poses a problem that an effective blood level of tulobuterol cannot be maintained for a sufficiently long time period.
For obtaining a satisfactory efficacy duration, it is necessary to administer the drug in an increased amount, for example, by increasing the thickness of the plaster layer containing tulobuterol dissolved therein, by heightening the content of tulobuterol, or by enlarging the area in which the plaster layer is in contact with the skin. However, these expedients pose the following problems: the patient comes to have an enhanced uncomfortable application feeling and the skin irritation is increased; the plaster layer comes to have reduced skin adhesive properties, so that peeling of the adhesive preparation from the skin occurs during application either partly at ends thereof or wholly; the blood level of the drug increases rapidly to produce severe side effects; and the adhesive preparation becomes more costly because the drug should be incorporated into a pressure-sensitive adhesive in an amount larger than the drug amount to be absorbed percutaneously. Thus, those expedients are not necessarily the best means.